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Biomedical subjects

K Mashiter

Publications and source records attributed to K Mashiter.

At least 37 records · Page 2Linked to original sources

Serum T4, T3, and TSH levels in primary hypothyroidism during replacement therapy with thyroxine.

Forty-five patients with primary hypothyroidism were studied during the first 4 to 36 months of replacement therapy with thyroxine. All became clinically euthyroid (23 patients while taking 0.1 mg/d, 14 patients while taking 0.15 mg/d, 7 patients while taking 0.2 mg/d, and 1 patient while taking 0.25 mg/d) over a period of three to six months. The patients were then divided for data analysis into two groups. Group I had normal serum T3 levels, normal (or elevated) serum T4 levels, and normal serum TSH levels. Group II had normal serum T3 levels, normal (or elevated) serum T4 levels, but high serum TSH levels. Group II was subdivided further into a group of 13 patients (group IIa) whose dose of thyroxine was deliberately increased until the serum TSH level was normalized; five of these patients became clinically and biochemically hyperthyroid. Group IIb consisted of eight patients with normal serum T3 and T4 levels and high serum TSH levels who were followed up without attempting to normalize their serum TSH levels. None became thyrotoxic, and their serum TSH levels showed little change. These findings suggest that serum TSH levels alone are not adequate to assess the required dose of thyroxine replacement therapy.

Female↗

Low-dose insulin infusion and substrate mobilization during surgery.

The effects of the i.v. infusion of insulin, 70 mu. kg-1h-1 for the first 60 min and 35 mu. kg-1h-1 subsequently, on the metabolic and endocrine responses to gynaecological surgery were investigated. In comparison with a control group of patients, the insulin infusion caused a marked decrease in circulating glucose, non-esterified fatty acids and beta-hydroxybutyrate concentrations, and an increase in blood lactate values. The plasma cortisol response to surgery was unaffected by the decrease in blood glucose, but the growth hormone response was increased. Heart rates and arterial pressures during surgery were not altered by the metabolic changes associated with insulin infusion, but there was a greater decrease in aural temperature. The results demonstrate the importance of insulin suppression during surgery in mediating changes in circulating metabolites.

Adult↗

Gonadotrophin and alpha subunit secretion by human 'functionless' pituitary adenomas in cell culture: long term effects of luteinizing hormone releasing hormone and thyrotrophin releasing hormone.

The long-term effects of LHRH and TRH on gonadotrophin alpha subunit, FSH and LH secretion by cell cultures of four human chromophobic pituitary tumours have been examined. The tumours derived from one male and three female patients who presented because of visual disturbance but had no evident endocrine symptoms. Subsequent serum hormone analysis showed the FSH to be high in the male but low or normal in the post-menopausal females whereas LH levels were low in all patients. In culture, basal hormone secretion could be maintained for periods up to 63 d. All tumours secreted alpha subunit and FSH, but much lower amounts of LH. Addition of LHRH or TRH for a period of 12 to 41 d showed that alpha subunit, FSH and LH secretion were stimulated by LHRH from one tumour, by LHRH and TRH from two tumours. There was always a rapid decline in the LH secretion. The tumour which secreted FSH predominantly was stimulated by TRH. We conclude that human pituitary 'functionless' adenomas can secrete gonadotrophin alpha subunit and FSH in vitro and that secretion can be stimulated during long term releasing hormone experiments. LH secretion, however, cannot be maintained.

Adenoma, Chromophobe↗

Lack of rise in serum prolactin following yttrium-90 interstitial irradiation for acromegaly.

We have investigated the possibility that the increase in serum PRL levels observed in patients with acromegaly treated with external irradiation could be due to damage to the hypothalamus or portal vessels, by comparing the effects of yttrium-90 interstitial irradiation, which is highly localised and does not normally extend to the hypothalamus, in a similar series of patients. Sixteen acromegalic patients treated by interstitial irradiation with yttrium-90 are described; GH fell from a mean of 131 mU/l (median 113 mU/l) to 17 mU/l (median 8 mU/l) after one year (P less than 0.001). PRL fell in the five initially hyperprolactinaemic patients (mean fall +/- SD: 39 +/- 17 micrograms/l at one year), but remained unchanged in the normoprolactinaemic group; PRL responsiveness to TRH was retained. Five, out of the seven normoprolactinaemic patients examined, were shown by in vitro studies of their pituitary biopsies, to have tumours that also synthesised or secreted PRL. These results are consistent with the hypothesis that the rise in PRL following external irradiation is the result of damage to the hypothalamus or portal vessels. A less likely explanation is that an overgrowth of radio-resistant PRL-secreting tumour cells is occurring after external irradiation, but not after yttrium-90 implantation.

Acromegaly↗

Hyperthyroidism due to a TSH secreting pituitary adenoma: case report, treatment and evidence for adenoma TSH by morphological and cell culture studies.

A 36-year-old woman with recurrent hyperthyroidism, inappropriately elevated serum TSH, and an 8 mm pituitary microadenoma is described. Transsphenoidal adenomectomy rapidly reduced serum TSH to normal and restored the euthyroid state with retention of other anterior pituitary functions. Tissue removed at operation was examined by light and electron microscopy and cell culture. The tissue was neoplastic, composed of irregular often elongated cells which immunostrained positively only with antisera to beta-TSH. The cells contained small granules (100-170 nm) usually along the cell membrane. In cell culture TSH alone was secreted and the rate of secretion declined with time. We conclude that the patient had a TSH secreting microadenoma as a cause of her hyperthyroidism.

Adenoma↗

Enteroglucagon and GIP after oral glucose in patients with prolactinoma and acromegaly.

We have performed oral glucose tolerance tests (OGTT) in nine patients with prolactinomas, eight patients with active acromegaly, five patients with acromegaly in remission and nine normal controls, and measured blood glucose, plasma insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide (GIP) and GH during the test. Patients with prolactinomas and with active acromegaly were hyperinsulinaemic and five of the nine patients with prolactinomas had impaired glucose tolerance, with blood glucose levels that were significantly higher than the normal controls. Prolactinoma patients had higher GIP levels than those with active acromegaly and both showed a failure of suppression of pancreatic glucagon. Of particular interest was the finding that enteroglucagon, a putative gut growth factor, was low in active acromegaly when compared with acromegaly in remission, but similar to normal in the rest of the patients.

Acromegaly↗

Prostatic cancer: treatment with long-acting LHRH analogue.

Fifteen patients with advanced carcinoma of the prostate were treated with a luteinising hormone releasing hormone agonist ICI 118 630. Three of 5 patients who had failed conventional hormone therapy have had a marked alleviation of bone pain, though no objective evidence of disease regression. Nine of 10 patients previously untreated have shown objective evidence of disease response. This drug appears to have advantages over conventional hormone therapy.

Aged↗

The effects of naloxone on circulating metabolites, glycoregulatory hormones and gut peptides during pelvic surgery.

The role of endogenous opioid peptides in mediating the endocrine and metabolic response to pelvic surgery was investigated. Fourteen patients were studied; seven were infused with the specific opioid antagonist, naloxone, at a rate of 20 micrograms kg-1 (body weight) hr-1, while the remainder acted as a control group. Naloxone exacerbated the glycaemic response to surgery but had no statistically significant effect on changes in the glycoregulatory hormones, pancreatic glucagon, insulin, cortisol and growth hormone. However, there was a wide individual variation in the glucagon response to naloxone with marked stimulation in some patients. Naloxone infusion increased plasma pancreatic polypeptide secretion during the 1st hour of surgery and reversed the decline in plasma motilin concentrations, but had no effect on circulating somatostatin, vasoactive intestinal polypeptide, gastrin, enteroglucagon and neurotensin values. We conclude that endogenous opioid peptides have only a limited role in modulating the endocrine and metabolic response to surgery.

Blood Glucose↗

Cushing's syndrome and depression--a prospective study of 26 patients.

Of 26 patients with active Cushing's syndrome assessed before and at three and 12 months after treatment, 21 had pituitary-dependent disease. Median urinary free cortisol values (per 24 hours) were 680, 180 and 200 nmol at zero, three and 12 months (normal less than 270 nmol), with significant improvement (P less than 0.001) at three and 12 months. Depression on the Hamilton rating scale was significantly less at three months (P less than 0.01) and at 12 months (P less than 0.001). We have already demonstrated that some patients with Cushing's syndrome have PSE diagnoses of depression and are more depressed than patients with other pituitary tumours. This is the firmest evidence to date that when Cushing's syndrome occurs it commonly causes depressive illness.

Adolescent↗

Effects of trifluoperazine on rat prolactin, growth hormone, thyroid stimulating hormone and adrenocorticotrophin secretion in vitro.

We have studied the effects of trifluoperazine, a proposed inhibitor of calmodulin directed cellular function, on adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), prolactin (Prl) and growth hormone (GH) secretion from primary cultures of rat adenohypophyseal cells. 5 X 10(-6)M and 10(-5)M trifluoperazine caused a significant (P less than 0.005) reversible dose-related decrease in basal Prl secretion but was less effective on basal GH secretion, significant reversible inhibition (P less than 0.005) occurring only with 10(-5)M. Trifluoperazine did not consistently alter basal ACTH or TSH secretion but did inhibit 10(-2)M theophylline stimulation of ACTH, Prl and GH secretion and 1.5 X 10(-7)M TRH stimulation of TSH and Prl secretion. Paradoxically 10(-5)M trifluoperazine enhanced theophylline stimulation of TSH secretion. Our results show trifluoperazine to have differential effects on Prl, GH, ACTH and TSH secretion, which are consistent with the known calcium dependence of pituitary hormone secretion and may suggest a role for calmodulin in this process.

Adrenocorticotropic Hormone↗

Insulin resistance and insulin deficiency in diabetic retinopathy of non-insulin-dependent diabetes.

To assess the role of insulin resistance and insulin deficiency in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus, 13 patients with and 12 patients without retinopathy were studied. The glucose clamp technique was used to measure insulin resistance and insulin response to glucose. During the euglycemic clamp, at comparable steady-state levels of glucose and insulin, the mean glucose infusion rate, which indicates the rate of glucose utilization, was lower in the retinopathy group than in the nonretinopathy group (6.1 +/- 0.5 versus 8.1 +/- 0.7 mg . kg-1 . min-1, P less than 0.02). Growth hormone (GH) concentrations were higher in the retinopathy group 8.4 +/- 2.5 versus 2.5 +/- 0.7 microIU/ml, P less than 0.05), but they did not correlate significantly with insulin resistance, expressed as mean glucose turnover. During the hyperglycemic clamp (+7 mmol/L above the fasting plasma glucose), the insulin response in the two groups of diabetics was similar. Increased insulin resistance represents an additional factor, which together with other factors, may be important in the pathogenesis of diabetic microvascular complications.

Blood Glucose↗

CT abnormalities of the pituitary in hyperprolactinaemic women with normal or equivocal sellae radiologically.

Sixteen young women with hyperprolactinaemia and normal or equivocal sella in radiographs underwent computed tomography using a Siemens Somatom II. In all but one case an abnormality was found. The sella was full in seven and partially empty in nine. A tumour was visible in six of the full and in four of the partially empty sellae. All but one of the 10 tumours was unilateral, and in seven the pituitary stalk was deviated away from the tumour. After administration of intravenous contrast (Urografin) four tumours showed diffuse enhancement, four ring enhancement, and two enhanced less than adjacent normal pituitary tissue. Two of the tumours have been subsequently shown histologically to be prolactinomas. Prolactin response to thyrotrophin-releasing hormone predicted a tumour in seven out of eight with visible tumours but also in three out of four without visible tumours; using metoclopramide, a tumour was predicted in six out of seven with tumours, but again in three out of four without visible tumours. Such results question the value of dynamic tests for the discrimination of tumours. We conclude that practically all women with sustained hyperprolactinaemia and a normal or equivocal sella radiologically have pituitary disease.

Adult↗

Successful treatment of Cushing's disease using yttrium-90 rods.

Interstitial irradiation using yttrium-90 (90Y) rods implanted by needle into the pituitary gland was used as primary treatment in 16 patients with pituitary dependent Cushing's disease. Clinical and biochemical remission was observed within three or six months in 13 and in the remaining three after a supplementary implant. There was no perioperative morbidity. Follow-up from the time of definitive operation ranged from six to 123 months (mean 39). No recurrence has been observed. The return of a normal diurnal cortisol rhythm has been observed in 10/12 patients studied after remission. Some form of long-term pituitary hormone replacement therapy was required in only the six patients who had received the largest irradiation dose. Implantation of 90Y is safe and effective treatment for patients with Cushing's disease, comparing favourably with selective trans-sphenoidal pituitary surgery.

Adolescent↗

Effect of acute hyperglycaemia on plasma potassium and aldosterone levels in type 2 (non-insulin-dependent) diabetes.

Potassium homeostasis during a 50-g oral glucose tolerance test was studied in 14 newly diagnosed, untreated Type 2 (non-insulin-dependent) diabetics. They showed a rise in plasma potassium from a mean +/- SEM basal of 3.9 +/- 0.1 to 4.4 +/- 0.1 mmol/l at 60 min and to 4.6 +/- 0.1 mmol/l at 90 min (p less than 0.01), whereas no change was seen in a group of 14 normal subjects. A possible role of mineralocorticoids was sought by measuring simultaneous serum aldosterone and deoxycorticosterone levels. Aldosterone was reduced after the glucose load in all subjects studied, falling to 73% of basal at 60 min in diabetics (p less than 0.01), and to 61% of basal at 90 min in normal subjects (p less than 0.001). Serum deoxycorticosterone showed a similar pattern. Thus it is unlikely that the rise in plasma potassium seen in the diabetic patients was due to abnormal levels of mineralocorticoids. Since the diabetic subjects were found to have an intact insulin response to the glucose load, it is suggested that resistance to insulin-stimulated potassium uptake into cells might be involved in the pathogenesis of the paradoxical hyperkalaemia induced by acute hyperglycaemia.

Aldosterone↗

Inappropriately low serum GH in an acromegalic: lysosomal involvement in intracellular hormone degradation.

A patient with galactorrhea, amenorrhae and severe acromegaly was found to have a large pituitary adenoma. In view of the severity of the disease the serum growth hormone (GH) level (22.5 mlU/liter) was considered inappropriately low. Tissue from the adenoma was obtained during successful treatment with interstitial irradiation. (90Yttrium). Trypsin-dispersed biopsy cells in culture for 12 days secreted low amounts of GH compared to the same number of adenoma cells from 5 other unselected acromegalics or a normal pituitary. No other hormones were secreted in culture. Immunocytochemical staining was positive only with GH antisera but showed low intracellular content. This was confirmed by direct analysis of the tumor tissue which showed the GH content to be only 20% of that found in 5 normal pituitaries and 4% of that found in 8 other adenomas from acromegalics. Electron microscopy showed a striking appearance, with GH secretory granules that were sparse in number, smaller than usual, and in the main arranged around numerous intracellular profiles with double membranes and low electron density that were tentatively identified as autophagic vacuoles (secondary lysosomes). Subcellular fractionation showed the distribution of the radioimmunoassayable GH in the gradient to be coincident with the peak of the lysosomes whereas in 2 other acromegalics the GH peak was clearly separated from the lysosomes. We conclude that the simultaneous appearance in our patient of the relatively low serum GH together with a large tumor and severe acromegaly can be explained biochemically by the striking finding of crinophagy - disposal of hormone secretory granules within the somatotroph cells themselves.

Acromegaly↗